Cancer cells copy migratory behavior and exchange signaling networks via extracellular vesicles

Abstract

Recent data showed that cancer cells from different tumor subtypes with distinct metastatic potential influence each other's metastatic behavior by exchanging biomolecules through extracellular vesicles (EVs). However, it is debated how small amounts of cargo can mediate this effect, especially in tumors where all cells are from one subtype, and only subtle molecular differences drive metastatic heterogeneity. To study this, we have characterized the content of EVs shed in vivo by two clones of melanoma (B16) tumors with distinct metastatic potential. Using the Cre‐LoxP system and intravital microscopy, we show that cells from these distinct clones phenocopy their migratory behavior through EV exchange. By tandem mass spectrometry and RNA sequencing, we show that EVs shed by these clones into the tumor microenvironment contain thousands of different proteins and RNAs, and many of these biomolecules are from interconnected signaling networks involved in cellular processes such as migration. Thus, EVs contain numerous proteins and RNAs and act on recipient cells by invoking a multi‐faceted biological response including cell migration.

A secreted pore‐forming protein modulates cellular endolysosomes to augment antigen presentation

“…EVs were purified as previously described with some modifications. 34 Briefly, BMDCs were cotreated with PBS, βγ-CAT (10 nM), OVA (100 μg/mL), or OVA plus βγ-CAT for 4 hours. The supernatants of the treated cells were collected and subjected to serial centrifugation (300 g for 20 minutes; 500 g for 20 minutes; 2000 g for 30 minutes) to remove dead cells and cell debris.…”

Emerging roles and therapeutic value of exosomes in cancer metastasis

“…Compelling evidence shows that exosomes can deliver functional molecules to acceptor cells, thereby promoting angiogenesis and increasing vascular leakage [33,34]. For example, one study has shown that exosomal miR-23a can induce angiogenesis in nasopharyngeal cancer [35].…”

Human milk extracellular vesicles target nodes in interconnected signalling pathways that enhance oral epithelial barrier function and dampen immune responses

“…Altogether this contributes to the versatile capacity of EVs to modulate cellular responses at multiple levels. The multi-faceted nature of EVs allows for the fine-tuning of complex signaling pathways in order to control the magnitude, kinetics and duration of cellular responses 10,11 . Previously, we have established an isolation procedure specifically designed for the reliable isolation of EVs from human milk 7 and performed in-depth proteomics analysis of milk EVs 5 .…”